Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lipocalin-type prostaglandin D synthase (L-PGDS) reportedly well predicts cardiovascular injuries in humans. However, little is known about the implications of L-PGDS in hypertension. In the present study, we investigated the alterations of serum and urinary L-PGDS in hypertensive patients with or without renal dysfunction. A total of 111 patients with hypertension (EHT; 65 with normoalbuminuria, 23 with microalbuminuria, 12 with macroalbuminuria, 11 with renal failure) and 102 normotensive, nomoalbuminuric subjects (NT) were studied. L-PGDS was measured by enzyme-linked immunosorbent assay, and L-PGDS in the kidney was localized using immunohistochemical methods. Blood pressure was higher in EHT groups than in the NT group (P<0.0001). There were no differences in age, gender, BMI, TC, TG, and HbA1c levels among the groups. Serum creatinine and urinary albumin levels were higher in the group with renal failure. Serum levels of L-PGDS were increased in EHT with normoalbuminuria, as compared with NT (0.88 +/- 0.05 versus 0.65 +/- 0.02 microg/mL; P<0.001). Serum levels of L-PGDS increased with the renal function worsened and positively correlated with serum creatinine, particularly in patients with renal impairments (r=0.76, P<0.0001). Similarly, the urinary L-PGDS excretions in EHT with normoalbuminuria were higher than that in NT (2.31 +/- 0.29 versus 1.16 +/- 0.14 mg/gCr, P<0.001), whereas there were no differences in urinary albumin excretion between the 2 groups. Moreover, urinary L-PGDS excretion increased dramatically with an increase in albuminuria or proteinuria. L-PGDS was stained in the tubules and the interstitium of the kidney in nephrosclerosis. In conclusion, patients with hypertension exhibited a higher level of L-PGDS in serum and urine, and this became increasingly obvious along with advance in renal dysfunction. These data suggest that L-PGDS metabolism is related to blood pressure and kidney injuries associated with hypertension.
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PMID:Lipocalin-type prostaglandin d synthase in essential hypertension. 1188 88

There is increasing evidence to suggest endothelial dysfunction as a critical factor in vascular diseases. Genetically predisposed spontaneously hypertensive rats (SHR) treated with inhibitors of nitric oxide (NO) synthase, develop a severe hypertensive nephrosclerosis without the necessity for surgical reduction in renal mass, nephrectomy, renal infarction or nephrotoxic drugs. In these animals, endothelial dysfunction is considered a valid model for assessment of the efficacy of cardiovascular therapy. SHR were treated with either the angiotensin-converting enzyme inhibitor enalapril or the angiotensin II (Ang II) AT(1)-receptor antagonist (AIIA) valsartan at sub-hypotensive doses and the effects on survival rates, cardiac and renal changes were monitored. Rats treated with valsartan, alone or in combination with enalapril, showed markedly higher survival rates (67-85%, respectively) than untreated animals (37%) or those treated with enalapril alone (55%). Valsartan at a dose which attenuated blood pressure increase led to even greater survival rates (95%). Despite these improved survival rates, at non-hypotensive doses the drugs had no effect on histological appearance, nor was kidney function improved. Plasma creatinine levels were reduced by valsartan, alone or in combination with enalapril, but proteinuria persisted with all treatments over the 12 weeks of the study. Aldosterone levels were significantly reduced by all treatments. The results suggest a beneficial role for endothelium in hypertension. Reduced renal perfusion pressure probably underlies the beneficial renal effects of high-dose valsartan.
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PMID:Combination of non-hypotensive doses of valsartan and enalapril improves survival of spontaneously hypertensive rats with endothelial dysfunction. 1196 7

Recently, we have shown that treatment of stroke-prone spontaneously hypertensive rats with angiotensin inhibitors for a limited time-window before puberty results in an attenuation of hypertensive nephrosclerosis in later life. The aim of this study was to examine the applicability of this therapeutic paradigm to a low-renin model. Dahl salt-sensitive (Dahl-S) rats were fed a high-salt diet from age 6 weeks. Some rats were treated with the angiotensin receptor blocker (ARB) candesartan cilexetil (2 mg/kg/d) from weaning to puberty (age 3-10 weeks), whereas other rats were treated continuously until overt renal damage was seen (age 3-16 weeks). Dahl-S rats on a high salt diet had increased blood pressure (207 +/- 3 vs. 125 +/- 2 mm Hg), proteinuria, and glomerular/vascular histological changes. The prepubertal treatment with ARB resulted in a continued suppression of blood pressure (153 +/- 2 mm Hg) at 16 weeks. Both proteinuria and renal histological changes were significantly (p < 0.05) attenuated, but not completely prevented by the treatment. No significant differences in plasma renin activity, renin mRNA, or AT1/AT2 mRNA were seen between groups. These results suggest that prepubertal treatment affords sustained renoprotection, even in an animal model with a suppressed renin-angiotensin system, and support the notion that appropriate prepubertal intervention may lead to a partial attenuation in the susceptibility to inherited renal diseases.
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PMID:Prepubertal treatment with angiotensin receptor blocker causes partial attenuation of hypertension and renal damage in adult Dahl salt-sensitive rats. 1213 77

Epidemiological data have suggested that the incidence of hypertensive nephrosclerosis is increasing despite the development of newer drug treatments. Recently, we studied the effects of temporary treatment of prepubescent rats with angiotensin receptor blocker (ARB) on the development of hypertensive nephrosclerosis in later life. Studies were performed using stroke-prone spontaneously hypertensive rats(SHRSP) and Dahl salt-sensitive rats(Dahl-S). In the case of SHRSP, treatment with ARB or angiotensin converting enzyme inhibitor(ACEI) from weaning to puberty(3 to 10 weeks) resulted in a continued reduction of blood pressure, and attenuation of proteinuria and renal histological changes at 30 weeks. In the case of Dahl-S, the prepubertal treatment with ARB caused a partial, but statistically significant reduction in proteinuria and renal damage. These results may be relevant for understanding the mechanisms of development of hypertension and hypertensive renal damage in these animal models.
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PMID:[Prevention of hypertensive renal damage by prepubertal treatment with ARB]. 1239 92

In the past few years diabetes has become the leading cause of end-stage renal disease in all Western countries. A correlation between blood pressure and rate of progression in diabetic nephropathy was noted very early, and increased local activity of the renin angiotensin system was identified as a major pathophysiological mechanism for proteinuria and nephrosclerosis in diabetic patients. Angiotensin converting enzyme (ACE) inhibitors have been shown to slow progression of nephropathy in type 1 diabetic patients. The majority of diabetic patients with nephropathy, however, are suffering from type 2 diabetes and until last year there was no convincing evidence of ACE inhibitors being able to slow progression in type 2 diabetic patients with nephropathy. Three new studies now fill this gap, showing that angiotensin receptor blockers (ARB) are nephroprotective in patients with type 2 diabetes, independently of blood pressure. This review provides an in-depth discussion of the results of these studies and provides recommendations for patient management.
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PMID:Angiotensin receptor antagonists in patients with nephropathy due to type 2 diabetes. 1255 90

An interim analysis of the AASK trial at three years demonstrates a renoprotective effect [slower decline in glomerular filtration rate (GFR), delayed onset of significant decrease in GFR, end-stage renal disease (ESRD) or death, and a decrease in urinary protein excretion] of the angiotensin converting enzyme (ACE) inhibitor, ramipril, as compared to the dihydropyridine calcium channel blocker (DHP-CCB), amlodipine, in patients with mild-to-moderate renal insufficiency. The beneficial effect occurred in the presence of similar levels of blood pressure control and was apparent in patients with proteinuric (beyond the threshold of "dipstick positive" proteinuria, 300 mg/day) and non-proteinuric hypertensive nephrosclerosis. At the time of the interim analysis, the effectiveness of the beta-blocker metoprolol was not significantly different from that of the ACE inhibitor. The data suggest that DHP-CCBs should be used with caution in the presence of mild-to-moderate renal insufficiency.
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PMID:ACE inhibition is effective and renoprotective in hypertensive nephrosclerosis: the African American Study of Kidney Disease and Hypertension (AASK) trial. 1286 79

There are many different glomerular disorders, including glomerulonephritis, diabetic nephropathy, and hypertensive nephrosclerosis. However, once glomerular damage reaches a certain threshold, the progression of renal disease is consistent and irreversible. Recent studies emphasized the crucial role of tubulointerstitial injury as a mediator of progression of kidney disease. One common mechanism that leads to renal failure via tubulointerstitial injury is massive proteinuria. Accumulating evidence suggests critical effects of filtered macromolecules on tubular cells, including lysosomal rupture, energy depletion, and tubular injury directly induced by specific components such as complement components. Another common mechanism is chronic hypoxia in the tubulointerstitium. Tubulointerstitial damage results in the loss of peritubular capillaries, impairing blood flow delivery. Interstitial fibrosis also impairs oxygen diffusion and supply to tubular cells. This induces chronic hypoxia in this compartment, rendering a vicious cycle. Development of novel therapeutic approaches against these final common pathways will enable us to target any types of renal disease.
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PMID:Mechanisms of tubulointerstitial injury in the kidney: final common pathways to end-stage renal failure. 1496 74

Here we report a community-based epidemiologic study of patients who received renal biopsy in Okinawa, Japan between 1967 and 1994. The total number of cases was 2832 (1395 men and 1437 women), and the mean (SD) age at biopsy was 30.0 (10.0) years (range 1.0 to 88.0 years). The most common clinical indications for renal biopsy were proteinuria/hematuria (46.7%), nephrotic syndrome (21.2%), acute glomerulonephritis (10.1%), and systemic lupus erythematosus (7.5%). Patients who received renal biopsy between 1985 and 1994 (N= 1480) were much less likely to have acute glomerulonephritis than patients treated between 1967 and 1984 (N= 1352); the rates of proteinuria/hematuria, renal failure, and diabetes mellitus were slightly higher in the later period. Okinawa patients who began dialysis between 1971 and 2000 (N= 5246) were also studied. Among them, a total of 468 patients (260 men and 208 women) began dialysis after renal biopsy. The cumulative incidence of end-stage renal disease (ESRD) among these patients was 17% in 17 years. Half of these patients developed ESRD in the 5.8 years after renal biopsy. Among the dialysis patients, the biopsy rate was 12.6% in chronic glomerulonephritis, 1.7% in diabetes mellitus, 2.6% in nephrosclerosis, and 52.1% in systemic lupus erythematosus. The diagnoses of primary renal diseases were primarily made clinically. The survival rate after starting dialysis therapy was slightly better in those with than in those without renal biopsy but this finding was not statistically significant (adjusted hazards ratio 0.855, 95% CI 0.711-1.028, P= 0.095). The clinical significance of renal biopsy, other than its provision of histologic evidence, remains to be shown.
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PMID:Outcome study of renal biopsy patients in Okinawa, Japan. 1532 81

Proteinuria is a known risk factor for both renal disease progression and cardiovascular morbidity and mortality in hypertensive populations. African Americans are among the highest risk groups for development of renal disease in the setting of hypertension and suffer a disproportionate burden of end-stage renal disease attributed to hypertension. Population-based studies indicate that African Americans have higher rates of albuminuria compared to non-African Americans in part due to higher rates of hypertension and diabetes in African Americans as compared to non-Hispanic whites for example. The African American Study of Kidney Disease and Hypertension (AASK) Trial was a prospective long-term clinical trial that examined the effect of aggressive blood pressure lowering versus usual blood pressure lowering in three different classes of antihypertensives on renal outcomes in approximately 1200 African Americans with hypertensive nephrosclerosis. Two thirds of trial participants had < 300 mg protein, and one third had > or = 300 mg of protein in a 24-hour urine specimen at baseline. Those with > 300 mg protein excretion compared to those with < 300 mg protein excretion at baseline had more rapid decline in renal function and ESRD events. Moreover, lower levels of proteinuria than previously thought may be important for identifying those at higher risk for kidney disease progression. The AASK cohort study, a follow-up to the trial, is now underway. The longer term follow-up will provide new insights into proteinuria and other risk factors for progression of kidney disease in hypertensive nephrosclerosis.
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PMID:Proteinuria and hypertensive nephrosclerosis in African Americans. 1548 98

A growing interest in the investigation of renal function has developed in recent years in big trials. This is justified by the high prevalence of nephrosclerosis as a cause of end-stage renal disease and the capacity of minor alterations of renal function to predict poor outcome for the patients. The finding of a small increase in serum creatinine values, a diminished estimated glomerular filtration rate, microalbuminuria and/or proteinuria, heralds a significant elevation in cardiovascular events and death as well as in total mortality. This paper describes the detection, prevalence and relevance of minor alterations in the stratification of cardiovascular risk in the hypertensive patient.
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PMID:Renal endpoints in hypertension trials. 1570 26


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